上颌窦鳞状细胞癌组织中p27蛋白和增殖细胞核抗原表达及其临床意义
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摘要
为探讨上颌窦鳞状细胞癌与抑癌基因p27和增殖细胞核抗原（PCNA）表达及其临床意义，对上颌窦鳞癌35例，其中高分化鳞癌12例、中分化鳞癌10例、低分化鳞癌13例，鼻腔鼻窦内翻性乳头状瘤15例进行了研究。
本文采用免疫组化方法检测了上颌窦鳞癌和内翻性乳头状瘤组织中p27蛋白和PCNA的表达，并与HE染色方法相比较。
结果显示，p27蛋白在上颌窦鳞癌组病人中阳性表达率为25.71%（9/35），而在对照组鼻腔鼻窦内翻性乳头状瘤组中的阳性率为73.33%（11/15），两组之间差异有极显著意义（P＜0.01）。但在上颌窦鳞癌高、中、低分化三组之间差异无显著意义（P＞0.05）。PCNA指数在两组病变间存在极显著性差异（P＜0.01），而且不同分化程度上颌窦鳞癌的三组间PCNA指数亦有显著性差异（P均＜0.05）。p27蛋白阳性与p27蛋白阴性病人的PCNA指数差异有显著性（P＜0.01）。
结果表明，p27和PCNA检测有助于更准确地估计上颌窦鳞癌及内翻性乳头状瘤的生物学特性，更有效的反映了上颌窦鳞癌的增殖活性。两个指标综合检测有助于上颌窦鳞癌的诊断，有助于上颌窦鳞癌恶性程度的估计，为上颌窦鳞癌的预后判断和临床治疗提供参考。
In this study, p27 protein and PCNA in maxillary sinus squamous cell carcinoma (MSCC) were examined with immunohistochemical method, and compared with HE staining. We tried to found out the relationship between MSCC and the expression of p27 protein and PCNA, so as to find a way to help diagnose early the malignant tumour and make clear its degree of differentiation.
Fifty paraffin sections of 50 patients were studied, among which were 35 maxillary sinus squamous cell carcinomas and 15 inverted papillomas of nasal sinus (NIP) as the control group. Among MSCC, there were 13 well differentiation, 10 moderate differentiation and 12 poor differentiation. All the samples were provided by the Department of Pathology of Affiliated Hospital of Qingdao University Medical College, and were diagnosed by at least two skilled pathologists.
The rate of p27 protein positive staining in MSCC was 25.71% (well differentiated MSCC, 25.0%; moderately differentiated MSCC, 30.0%; poorly differentiated MSCC, 23.1%). Furthermore ，11 of 15 NIP showed p27 protein positive staining. Significant difference was found between MSCC and NIP (P＜0.01)，but there was no significance among well, moderately and poorly differentiated MSCC（P＞0.05）.MSCC had more PCNA positive cells than NIP. There was significant difference between random differentiated groups of MSCC（P＜0.05）.The results indicated the proliferating activities of benign or malignant tumours of maxillary sinus and various differentiated MSCC. The expression of p27 protein and the reduction of PCNA labeled index(PCNA LI) had significant difference（P＜0.01）.
The study proved that p27 and PCNA could help evaluate the clinicopathological characteristics of MSCC and NIP, and they can be important factors to reflect the proliferating activity of MSCC. The two factors confined the evidences to predict the prognosis and treat the disease.
本文采用免疫组化方法检测了上颌窦鳞癌和内翻性乳头状瘤组织中p27蛋白和PCNA的表达，并与HE染色方法相比较。
结果显示，p27蛋白在上颌窦鳞癌组病人中阳性表达率为25.71%（9/35），而在对照组鼻腔鼻窦内翻性乳头状瘤组中的阳性率为73.33%（11/15），两组之间差异有极显著意义（P＜0.01）。但在上颌窦鳞癌高、中、低分化三组之间差异无显著意义（P＞0.05）。PCNA指数在两组病变间存在极显著性差异（P＜0.01），而且不同分化程度上颌窦鳞癌的三组间PCNA指数亦有显著性差异（P均＜0.05）。p27蛋白阳性与p27蛋白阴性病人的PCNA指数差异有显著性（P＜0.01）。
结果表明，p27和PCNA检测有助于更准确地估计上颌窦鳞癌及内翻性乳头状瘤的生物学特性，更有效的反映了上颌窦鳞癌的增殖活性。两个指标综合检测有助于上颌窦鳞癌的诊断，有助于上颌窦鳞癌恶性程度的估计，为上颌窦鳞癌的预后判断和临床治疗提供参考。
In this study, p27 protein and PCNA in maxillary sinus squamous cell carcinoma (MSCC) were examined with immunohistochemical method, and compared with HE staining. We tried to found out the relationship between MSCC and the expression of p27 protein and PCNA, so as to find a way to help diagnose early the malignant tumour and make clear its degree of differentiation.
Fifty paraffin sections of 50 patients were studied, among which were 35 maxillary sinus squamous cell carcinomas and 15 inverted papillomas of nasal sinus (NIP) as the control group. Among MSCC, there were 13 well differentiation, 10 moderate differentiation and 12 poor differentiation. All the samples were provided by the Department of Pathology of Affiliated Hospital of Qingdao University Medical College, and were diagnosed by at least two skilled pathologists.
The rate of p27 protein positive staining in MSCC was 25.71% (well differentiated MSCC, 25.0%; moderately differentiated MSCC, 30.0%; poorly differentiated MSCC, 23.1%). Furthermore ，11 of 15 NIP showed p27 protein positive staining. Significant difference was found between MSCC and NIP (P＜0.01)，but there was no significance among well, moderately and poorly differentiated MSCC（P＞
The study proved that p27 and PCNA could help evaluate the clinicopathological characteristics of MSCC and NIP, and they can be important factors to reflect the proliferating activity of MSCC. The two factors confined the evidences to predict the prognosis and treat the disease.
引文
1. 黄选兆，汪吉宝主编. 实用耳鼻咽喉科学. 北京:人民卫生出版社,1998.279～282
2. 尹凤兰，庞康，罗红岩. 鼻腔鼻窦恶性肿瘤临床治疗分析. 耳鼻咽喉-头颈外科 1999.04.15; 6(2): 77-79
3. 樊忠,王天铎主编. 实用耳鼻咽喉科学. 济南:山东科学技术出版社,1996.392～398
4. 陈惠黎. 肿瘤的发病机理. 见:汤钊猷主编.现代肿瘤学.上海:上海医科大学出版社. 1995:140
5. Hlavcak P, Sedlakova O, Sedlak J, et al. Cell surface immunophenotype and gelatinase activity of the human breast carcinoma cell line (MCF-7/6) with unctionally defective Ecadherin.Neoplasma, 1999,46(1):12
6. Saegusa-M; Nitta-H; Hashimura-M;et al. Down-regulation of p27Kip1 expression is correlated with increased cell proliferation but not expression of p21waf1 and p53, and human papillomavirus infection in benign and malignant tumours of sinonasal regions. Histopathology. 1999 Jul; 35(1): 55-64
7. 黄选兆主编. 耳鼻咽喉科学. 北京：人民卫生出版社,1995:69-70
8. Demers-PA, Kogevinas-M, Boffetta-P, et al. Wood dust and sino-nasal cancer: pooled reanalysis of twelve case-control studies. Am-J-Ind-Med. 1995 Aug; 28(2): 151-66
9. Leclerc-A,Martinez-Cortes-M,Gerin-M,et al. Sinonasal cancer and wood dust exposure: results from a case-control study. Am-J-Epidemiol. 1994 Aug 15; 140(4): 340-9
10. Battista-G, Comba-P, Orsi-D, et al. Nasal cancer in leather workers: an occupational disease [editorial] [published erratum appears in J Cancer Res Clin Oncol 1995;121(5):320] J-Cancer-Res-Clin-Oncol. 1995; 121(1): 1-6
11. Fu-H, Demers-PA, Costantini-AS, et al. Cancer mortality among shoe manufacturing workers: an analysis of two cohorts. Occup-Environ-Med. 1996 Jun; 53(6): 394-8
12. Leung-SY,Yuen-ST,Chung-LP, et al. Epstein-Barr virus is present in a wide histological spectrum of sinonasal carcinomas. Am-J-Surg-Pathol. 1995 Sep; 19(9): 994-1001
13. Cayrol-C, Flemington-EK. The Epstein-Barr virus bZIP transcription factor Zta causes G0/G1 cell cycle arrest through induction of cyclin-dependent kinase inhibitors. EMBO-J. 1996 Jun 3; 15(11): 2748-59
14. Caruana-SM, Zwiebel-N, Cocker-R，et al. p53 alteration and human papilloma virus infection in paranasal sinus cancer. Cancer. 1997 Apr 1; 79(7): 1320-8
15.Torahiko Nakashi，Tadashi Nakashi , Muneyuki Masuda, et al. p53 and bcl-2 expression and argyrophilic nucleolar organizer regions in patients with malignant maxillary sinus tumours. The Journal of Laryngology and Otology .January 1997,Vol.111,38-42
16. Halvorson-DJ, Day-S, Christian-DR Jr, et al. Flow cytometry and squamous cell carcinoma of the maxillary sinus: A possible prognostic indicator for multimodality intervention. Oncology. 1999 Apr; 56(3): 248-52
17. Miyaguchi-M, Kawahara-T, Sakai-S, et al. A correlation of argyrophilic nucleolar organizer regions with prognoses in patients with maxillary sinus squamous cell carcinoma. Eur-Arch-Otorhinolaryngol. 1994; 251(4): 229-32
18. 孙彦,吕向光. 上颌窦鳞状细胞癌核仁组成区相关嗜银蛋白的检测. 河北医学 1996.05.30;2(3):196-197
19. 朱德民,王纾宜,王薇,等. 上颌窦鳞癌两种癌基因及增殖细胞核抗原的表达及意义. 中华耳鼻咽喉科杂志 1998.04.10; 33(2): 94-96
20. Poly K，Kato J, Solomon M，et al. p27Kip1, a cyclin-CDK inhibitor;links transforming growth factor-β and contact inhibition to cell cycle arrest. Genes Dev, 1994,8:9-22
21. Poly K, Lee MH, Erjument BH, et al. Cloning of p27kip1、a cyclin-dependent kinase inhibitor and a potential mediator of extracellular antimitogenic signals. Cell,1994,78:59
22. Toyoshima H, Hunter T. p27, a novel inhibitor of G1 cyclin-cdk protein kinase activity is related to p21. Cell, 1994,78:67
23. Pietenpol JA, Bohalander SK, Sato Y, et al. Assignment of the human p27kip1 gene to 12p13 and its analysis in leukemias. Cancer Res, 1995,55:1206
24. 江虹,王永潮. 哺乳类细胞中周期蛋白依赖激酶抑制因子. 生物科学进展 1996.04.25;27(2):107-112
25.Fero ML, Rivkin M, Tasch M, et al. A syndrome of multiorgan hyperplasia with features of gigantism, tumorigenesis, and female sterility in p27(kip1)-deficient mice. Cell,1996,85: 733-744
26. 刘平湖，童坦君. 细胞周期负调控. 细胞生物学杂志 1996.12.15; 18(4):49-153
27. Cariou-S; Catzavelos-C; Slingerland-JM . Prognostic implications of expression of the cell cycle inhibitor protein p27Kip1. Breast-Cancer-Res-Treat. 1998; 52(1-3): 29-41
28. Kawamata N， Morosetli R， Miller CW， et al. molecular analysis of the cyclin-dependent kinase inhibitor gene p27kip1 in human malignancies ［J］. Cancer Research,1995,55(11):2266-9
29. Konstantin S, Jean F, Takeachi S, et al. p27kip1 mutation found in breast cancer［J］.Cancer Research,1996,56(10):2400
30. 罗昆仑. p27与细胞周期调控. 国外医学·肿瘤学分册 1998.10.08; 25(5): 262-265
31. 曹红亮,陈爱军,张广德,等. p27蛋白在乳腺癌中的表达及其意义.实用癌症杂志. 2000.5;15(3):276-278
32. 王福生,蒋丹斌,宋怀宇,等. p27kip1在胃癌中的表达及与临床病理分期和预后的关系. 癌症.2000,19(5):495
33. 王洪乾,洪东旭. p27癌基因蛋白在肝癌和癌旁肝组织中表达的意义研究.实用肿瘤杂志.2000,15(3):155-156
34. Puay T, Cady B, Wamer M, et al. The cell cycle inhibitor p27 is an independent prognostic marker in small(T1aTb) invasive breast carcinomas（J）。Cancer Research， 1997，57（7）：1259
35. Fan-GK; Fujieda-S; Sunaga-H; et al. Expression of protein p27 is associated with progression and prognosis in laryngeal cancer. Laryngoscope. 1999 May; 109(5): 815-20
36. Ohashi-Y, Sasano-H, Yamaki-H, et al. Cell cycle inhibitory protein p27 in esophageal squamous cell carcinoma. Anticancer-Res. 1999May-Jun;19(3A):1843-8
37. Migachi K. Autoantibody to a nuclear antigen in proliferating cells. Journal of Immunology, 1978;121:2228
38. Bravo R，Frank R，Blundell PA，et al. Cyclin/PCNA is the auxillary protein of DNA polymerase-delta .Nature, Pathol,1987,326:515
39. Chan AT, Ho S, Teo PM, et al. Assesment of proliferating cell nuclear antigen in nasopharyngeal carcinoma tissue and its relation to clinical findings. Oral-Oncol.1997 Jan;33(1):13-8
40. 罗晓晋,甘晓榕,米秀玲. 增殖细胞核抗原在口腔鳞状细胞癌中的表达.山西医科大学学报 1997.09.26;28(3):172-173
41. Kuwano-H, Saeki-H，Kawaguchi-H, et al. Proliferative active of cancer cells in front and center areas of carcinoma in situ and invasive sites of esophageal squamous-cell carcinoma. Int-Cancer. 1998 Oct 5;78(2);149-52
42. 肖自安,罗勇,曾益慈. 喉鳞癌中增殖细胞核抗原和p53蛋白表达的临床意义及其相互关系. 中国耳鼻咽喉颅底外科杂志 1997.06.30;3(2):103-106
43. 三国尚志,福田论古田康,他. 抗PCNA抗体を用ぃを上颚洞癌の细胞增殖能と预后の检讨.日耳鼻,1992,95:1944
44. Wolf-DC, Gross-EA, Lyght-O, et al. Immunohistochemical localization of p53, PCNA, and TGF-alpha proteins in formaldehyde-induced rat nasal squamous cell carcinomas. Toxicol-Appl-Pharmacol. 1995 May; 132(1): 27-35
45. 魏永昆,高延昭,许平,等. 上颌窦乳头状瘤及鳞状细胞癌增殖细胞核抗原的表达. 河南医科大学学报 1997.06.15;32(2):34-37
46. Goubin F, Ducommun B. Identification of binding domains on the p21CIP1 cylin dependent. Oncogene, 1995,10:2281
2. 尹凤兰，庞康，罗红岩. 鼻腔鼻窦恶性肿瘤临床治疗分析. 耳鼻咽喉-头颈外科 1999.04.15; 6(2): 77-79
3. 樊忠,王天铎主编. 实用耳鼻咽喉科学. 济南:山东科学技术出版社,1996.392～398
4. 陈惠黎. 肿瘤的发病机理. 见:汤钊猷主编.现代肿瘤学.上海:上海医科大学出版社. 1995:140
5. Hlavcak P, Sedlakova O, Sedlak J, et al. Cell surface immunophenotype and gelatinase activity of the human breast carcinoma cell line (MCF-7/6) with unctionally defective Ecadherin.
6. Saegusa-M; Nitta-H; Hashimura-M;et al. Down-regulation of p27Kip1 expression is correlated with increased cell proliferation but not expression of p21waf1 and p53, and human papillomavirus infection in benign and malignant tumours of sinonasal regions. Histopathology. 1999 Jul; 35(1): 55-64
7. 黄选兆主编. 耳鼻咽喉科学. 北京：人民卫生出版社,1995:69-70
8. Demers-PA, Kogevinas-M, Boffetta-P, et al. Wood dust and sino-nasal cancer: pooled reanalysis of twelve case-control studies. Am-J-Ind-Med. 1995 Aug; 28(2): 151-66
9. Leclerc-A,Martinez-Cortes-M,Gerin-M,et al. Sinonasal cancer and wood dust exposure: results from a case-control study. Am-J-Epidemiol. 1994 Aug 15; 140(4): 340-9
10. Battista-G, Comba-P, Orsi-D, et al. Nasal cancer in leather workers: an occupational disease [editorial] [published erratum appears in J Cancer Res Clin Oncol 1995;121(5):320] J-Cancer-Res-Clin-Oncol. 1995; 121(1): 1-6
11. Fu-H, Demers-PA, Costantini-AS, et al. Cancer mortality among shoe manufacturing workers: an analysis of two cohorts. Occup-Environ-Med. 1996 Jun; 53(6): 394-8
12. Leung-SY,Yuen-ST,Chung-LP, et al. Epstein-Barr virus is present in a wide histological spectrum of sinonasal carcinomas. Am-J-Surg-Pathol. 1995 Sep; 19(9): 994-1001
13. Cayrol-C, Flemington-EK. The Epstein-Barr virus bZIP transcription factor Zta causes G0/G1 cell cycle arrest through induction of cyclin-dependent kinase inhibitors. EMBO-J. 1996 Jun 3; 15(11): 2748-59
14. Caruana-SM, Zwiebel-N, Cocker-R，et al. p53 alteration and human papilloma virus infection in paranasal sinus cancer. Cancer. 1997 Apr 1; 79(7): 1320-8
15.
16. Halvorson-DJ, Day-S, Christian-DR Jr, et al. Flow cytometry and squamous cell carcinoma of the maxillary sinus: A possible prognostic indicator for multimodality intervention. Oncology. 1999 Apr; 56(3): 248-52
17. Miyaguchi-M, Kawahara-T, Sakai-S, et al. A correlation of argyrophilic nucleolar organizer regions with prognoses in patients with maxillary sinus squamous cell carcinoma. Eur-Arch-Otorhinolaryngol. 1994; 251(4): 229-32
18. 孙彦,吕向光. 上颌窦鳞状细胞癌核仁组成区相关嗜银蛋白的检测. 河北医学 1996.05.30;2(3):196-197
19. 朱德民,王纾宜,王薇,等. 上颌窦鳞癌两种癌基因及增殖细胞核抗原的表达及意义. 中华耳鼻咽喉科杂志 1998.04.10; 33(2): 94-96
20. Poly K，Kato J, Solomon M，et al. p27Kip1, a cyclin-CDK inhibitor;links transforming growth factor-β and contact inhibition to cell cycle arrest. Genes Dev, 1994,8:9-22
21. Poly K, Lee MH, Erjument BH, et al. Cloning of p27kip1、a cyclin-dependent kinase inhibitor and a potential mediator of extracellular antimitogenic signals. Cell,1994,78:59
22. Toyoshima H, Hunter T. p27, a novel inhibitor of G1 cyclin-cdk protein kinase activity is related to p21. Cell, 1994,78:67
23. Pietenpol JA, Bohalander SK, Sato Y, et al. Assignment of the human p27kip1 gene to 12p13 and its analysis in leukemias. Cancer Res, 1995,55:1206
24. 江虹,王永潮. 哺乳类细胞中周期蛋白依赖激酶抑制因子. 生物科学进展 1996.04.25;27(2):107-112
25.
26. 刘平湖，童坦君. 细胞周期负调控. 细胞生物学杂志 1996.12.15; 18(4):49-153
27. Cariou-S; Catzavelos-C; Slingerland-JM . Prognostic implications of expression of the cell cycle inhibitor protein p27Kip1. Breast-Cancer-Res-Treat. 1998; 52(1-3): 29-41
28. Kawamata N， Morosetli R， Miller CW， et al. molecular analysis of the cyclin-dependent kinase inhibitor gene p27kip1 in human malignancies ［J］. Cancer Research,1995,55(11):2266-9
29. Konstantin S, Jean F, Takeachi S, et al. p27kip1 mutation found in breast cancer［J］.Cancer Research,1996,56(10):2400
30. 罗昆仑. p27与细胞周期调控. 国外医学·肿瘤学分册 1998.10.08; 25(5): 262-265
31. 曹红亮,陈爱军,张广德,等. p27蛋白在乳腺癌中的表达及其意义.实用癌症杂志. 2000.5;15(3):276-278
32. 王福生,蒋丹斌,宋怀宇,等. p27kip1在胃癌中的表达及与临床病理分期和预后的关系. 癌症.2000,19(5):495
33. 王洪乾,洪东旭. p27癌基因蛋白在肝癌和癌旁肝组织中表达的意义研究.实用肿瘤杂志.2000,15(3):155-156
34. Puay T, Cady B, Wamer M, et al. The cell cycle inhibitor p27 is an independent prognostic marker in small(T1aTb) invasive breast carcinomas（J）。Cancer Research， 1997，57（7）：1259
35. Fan-GK; Fujieda-S; Sunaga-H; et al. Expression of protein p27 is associated with progression and prognosis in laryngeal cancer. Laryngoscope. 1999 May; 109(5): 815-20
36. Ohashi-Y, Sasano-H, Yamaki-H, et al. Cell cycle inhibitory protein p27 in esophageal squamous cell carcinoma. Anticancer-Res. 1999
37. Migachi K. Autoantibody to a nuclear antigen in proliferating cells. Journal of Immunology, 1978;121:2228
38. Bravo R，Frank R，Blundell PA，et al. Cyclin/PCNA is the auxillary protein of DNA polymerase-delta .Nature, Pathol,1987,326:515
39. Chan AT, Ho S, Teo PM, et al. Assesment of proliferating cell nuclear antigen in nasopharyngeal carcinoma tissue and its relation to clinical findings. Oral-Oncol.1997 Jan;33(1):13-8
40. 罗晓晋,甘晓榕,米秀玲. 增殖细胞核抗原在口腔鳞状细胞癌中的表达.山西医科大学学报 1997.09.26;28(3):172-173
41. Kuwano-H, Saeki-H，Kawaguchi-H, et al. Proliferative active of cancer cells in front and center areas of carcinoma in situ and invasive sites of esophageal squamous-cell carcinoma. Int-Cancer. 1998 Oct 5;78(2);149-52
42. 肖自安,罗勇,曾益慈. 喉鳞癌中增殖细胞核抗原和p53蛋白表达的临床意义及其相互关系. 中国耳鼻咽喉颅底外科杂志 1997.06.30;3(2):103-106
43. 三国尚志,福田论古田康,他. 抗PCNA抗体を用ぃを上颚洞癌の细胞增殖能と预后の检讨.日耳鼻,1992,95:1944
44. Wolf-DC, Gross-EA, Lyght-O, et al. Immunohistochemical localization of p53, PCNA, and TGF-alpha proteins in formaldehyde-induced rat nasal squamous cell carcinomas. Toxicol-Appl-Pharmacol. 1995 May; 132(1): 27-35
45. 魏永昆,高延昭,许平,等. 上颌窦乳头状瘤及鳞状细胞癌增殖细胞核抗原的表达. 河南医科大学学报 1997.06.15;32(2):34-37
46. Goubin F, Ducommun B. Identification of binding domains on the p21CIP1 cylin dependent. Oncogene, 1995,10:2281